We are the brain, we are the neurons...

[Mars Man]

Parkinson's Disease

Parkinson's Disease (PD) does have a genetically traced cause in some cases, although it is not like Huntington's Disease which is fully hereditary in nature. (1). While dopamine problems are one major factor in PD, there are in other cases, also other factors such genetic mutation of PARK2 (on chromosome 6q25.2-q27), or Lewy body build up.

The symptoms of PD are not only the rigid, 'cog wheel' motion, mask-like facial elongation, and resting tremors, but also cognitive deficiencies, changes in memory retention, and in some cases sexual disposition alterations. (2)

What has been studied, understood well enough to make sound conclusions and theories on, give us the build/state of brain which is the result seen from the third person perspective (3P). Neurons (as well as some glia) project. The neurons project the axons to synapse onto other neurons, or (at times) to themselves. In that the build/state, and 'conscious' (that is the placeholder term for the activity that this class of excitable cell is) is produces results through the projection of axons, we can say that the 3P observation (both generally and through finely tuned testing) which is that of the PD circumstance, state of being and mind, and behavior, is that which is projected by the particular brain build/state.

Especially in early on-set PD, we can see how by the fourth decade, or so, this is condition is the individual. Even though deep brain stimulation (DBS) and cell implantation can reverse some of the symptoms (as can L-Dopa and some other drugs can for some amount of time) this essential brain is just that brain, as is, and it is that which the PD patient is.

The mind is generally quite clear (evidently) in many cases up to some point of progression, but as noted above, often enough evidences minor deficits in cognitive perception and executive reasoning control. In some cases, at times, one could imagine it as being in a certain degree of locked-in state--brain cannot control body function as fully as can be imagined--since there will have been a time when full control had been there, almost always.

In summary on this point, PD is the build/state of the neuronal tissue of certain subcortical structures which project that condition in its particular fullness. This includes not only motor mechanisms, but also can affect, for more positive (as in creative increment), or negative (as in memory capability loss and cognitive acuity loss) aspects of general mental life and personhood.



1. Dawson, T.M., and Dawson V.L. (2003) Molecular Pathways of Neurodegeneration in Parkinson's Disease. Science 302, pp 819-821 (31 Oct).

Hattori, N., and Mizuno, Y. (2003) Parkinson's Disease. IN: Nature Encyclopedia of The Human Genome vol 4, pp 492-497.


2. Santangelo, G., et al. (2009) Anhedonia and cognitive impairment in Parkinson's disease: Italian validation of the Snaith-Hamiltom Pleasure Scale and its application in the clinical routine practice during the PRIAMO study. Parkinsonism and Related Disorders 15, pp 576-581.

Drago, V. et al. (2009) Artistic creativity and DBS: A case report. Journal of the Neurological Sciences 276, pp 138-142.

Park, K.H., et al., (2009) Strategic infarction dementia mimicking sudden cognitive and behavioral change induced by glubus pallidus infarction. (poster abstract) Journal of the Neurological Sciences 283(1-2), p 280.

Zanini, S. et al. (2009) Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: A pilot study. Parkinsonism and Related Disorders 15, pp 606-609.

Skeel, R.L. et al. (2001) Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease. Neuropsychologia 39, pp 962-971.

etc..

 

[Tsuyoiko]

I can speak on PD from personal experience, as my dad has had early-onset PD for about 6 or 7 years, with the initial symptoms appearing when he was 49/50. These first symptoms were very subtle, just a slight stiffness in the joints. It seems likely that there's an inherited component in his case, as two of his five siblings were fellow sufferers, although they both developed it in old age. However, the symptoms first began to show soon after a serious car accident, so we have wondered whether that contributed in any way.

The drugs (one of which is L-dopa, I forget the other), help a lot. Dad has learnt to manage his time around the drugs, planning activities for when he expects to be at his best. When an attack comes on, he just has to drop everything and rest, which has been the most difficult adjustment for him, resulting in his having to retire from his business early. Emotional stress is absolutely the worst trigger in his case. There has been a change in his personality. I'm not sure if it's a symptom of the disease, a side-effect of the drugs, or just my dad's way of coming to terms with the illness, but he is a lot more cheerful, laid-back and adventurous than he was before getting sick. Humour has been an important coping mechanism for him - he has a great collections of PD jokes!

 

[Mars Man]

Thanks for presenting your father's experience and dealing with PD, Tsuyoiko chan. My concern and heart go out for him. As I recall having read, it is considered that early on-set cases are the hereditary cases much more often than not, while late on-set cases most usually are not. The accident, however, may well have provided just the certain circumstances allowing some kind of internal feed forward event which, in turn, may have triggered the genetic disposition to kick in a bit earlier than if it had not happend--possibly.

There has been a change in his personality. I'm not sure if it's a symptom of the disease, a side-effect of the drugs, or just my dad's way of coming to terms with the illness, but he is a lot more cheerful, laid-back and adventurous than he was before getting sick. Humour has been an important coping mechanism for him - he has a great collections of PD jokes!

Yes, without saying anything in the way of possible side effects of PD, in your father's case, it is very good that the ability to be humorous and adventurous has gained in strength. I can kind of conceptualize just how hard, actually, maintaining such a mental position may be.

The one professor who I had done what we called 'Science Cafe' (here on campus) who also had early on-set, has shown cognitive decline to a small degree, and although he still comes to the uni these days, he has no responsibilities nor classes. He has not taken such a humorous position (or outlook) as your father has (although not out-right negative, either). In working with him, and (more recently) spending some time a lunch with him, I can really feel for the hardship in that. Due to his medication, the tremor has increased to the point of appearing to be affectd by Huntington's disease--dancing all around. Speech is almost undistinguishable, and having a conversation with him is hard, but I make an effort to do that from time to time because others do not !

As for the overall presentation of this thread, again, however, we find that the more often than should be overlooked element of the individual, the person, is the motor tissue of the individual's brain which also makes the person. As one would be, in neural projection before the onset of such a brain build/state, that brain, that same one is then 'this' brain in the stages of rebuilding/ resituating which project that. The conclusion is the same--we are the neurons (not in that most literal way of individual neurons alone, but through the synaptic connectivity and reentry processes of whole brain {inclusive of environmental/cultural embodiment}) The motor output of the patient with any degree of PD, is that person.

 

[Tsuyoiko]

The one professor who I had done what we called 'Science Cafe' (here on campus) who also had early on-set, has shown cognitive decline to a small degree, and although he still comes to the uni these days, he has no responsibilities nor classes. He has not taken such a humorous position (or outlook) as your father has (although not out-right negative, either). In working with him, and (more recently) spending some time a lunch with him, I can really feel for the hardship in that. Due to his medication, the tremor has increased to the point of appearing to be affectd by Huntington's disease--dancing all around. Speech is almost undistinguishable, and having a conversation with him is hard, but I make an effort to do that from time to time because others do not !

We haven't noticed any appreciable cognitive decline yet. There are occasional incidences of general forgetfulness and confusion, but it's not clear that they are symptoms of PD and not just the episodes of incomplete attention that we all get sometimes - that's how slight they are for the moment.

Dad's speech is slightly slurred, but not so noticeable as he's always been a bit of a mumbler. His medication isn't at a high enough dose yet to cause such debilitating side effects, although he does move around a lot in his sleep.

Since his progression has been quite slow so far, the hope that better treatments will be developed before he gets too bad keep us going somewhat.

The motor output of the patient with any degree of PD, is that person.

My dad understands that better than anyone. He owns the disease, he recognises it as part of himself, and he tries to see the positive in it - which is there, hard as that might be to believe.

 

[Mars Man]

That is a good commentary on the situation that you all there, in your immediate family, are in, Tsuyoiko chan, and towards my post. I do hope the same as you do, that progression will remain slow in your father's case, and that something will eventually come up which is much better, yet less invasive than electrode implantation.

With your last lines there, I felt a 'more power to you' emotion for your dad. Good for him !! Now, we need to work a little more (and I am especially speaking from the angle of Japanese society) at getting this much more into the general public knowledge arena. We had so very few students show up for our Science Cafe (even with some good posters and subject matter outlines [he's an astrophysicist who has done a fair amount of research on solar matters and inner space bodies, events, etc.] like solar plasma effects, hormonal love effects, sleep and memory consolidation [good for exams], and videos of meteor showers) because--as I theorize, and I think the evidence is there--students were afraid. They had no idea how to deal with the situation. They lacked knowledge of, not only brain matters, but of the potential brain matters in circumstances where the build/state is different from what we can call neuroanatomically, connectively (etc.) normal. Public education is a very honorable, and necessary pursuit.

 

[Tsuyoiko]

Public education is a very honorable, and necessary pursuit.

Absolutely agreed.

 

[Mars Man]

I greatly appreciate the backing and emotion, Tsuyoiko chan. Now, while I put together the summary for a post on Huntington's disease, I'd like to try to post a little entertainment. This is very good proteomic imaging work on a slice of mouse cerebral cortex. the mouse, being very much (not exactly, of course) like the human brain, has been very good in understanding how things can go wrong, and what possible lines of overcoming problems there are.

The source is Micheva, K.D, et al. (2010) Single-synapse analysis of a diverse synapse population: Proteomic imaging methods and markers. Neuron 68:639-653. The music score is by Catherine Rose Smith. In the upper left hand corner of the movie frame, there is a box showing where the close up focus frame is on the sheet. The layers and subcortical structures are identified in the lower right hand corner.

This is actually a very awe inspiring and thought provoking presentation...and the details provided in the study itself are very informative. The Smith lab at Standford is doing so good pioneering work. I hope I can get this thing to work...it's a YouTube thing.

 

[Mars Man]

Huntington's disease

In the general category of neurological spectrum of PD, we also have Huntington's disease (HD). HD, unlike PD which is not so commonly a genetically derived matter, is completely genetical in its root causes (1) The mutation of a vital gene product called a huntingtin (htt) results due to genetic defect on the dominant chromosome 4 (5' coding condon) in the form of multiple GAC repeats. While a normal person will have a range from around 10 to 34, the weaker cases of HD show from 39-50 repeats, while strong cases may repeat as much as up to 70 and above (usually childhood onset cases) (1, 2).

The basal ganglia area operates by much inhibition (GABA), and these projecting neurons are hit hard by the disease. Post mortem studies show that the caudate nuclei are affected the earliest and most severely as the disease progresses. In late stages, the caudate and putamen are almost completely destroyed, and neuronal loss can be found in layers 3, 5, and 6 of the cerebral cortex in areas. While more studies suggest that neuronal loss occurs somewhat equally all over the cortical sheet, a few studies have failed to find that--meaning we can think that (as is usually the case) that not all cases of cell death patterns are the same.

The more noticable symptom is the restlessness which resembles a mode of dancing (which had led to the earlier name Huntinton's Chorea. Uncontrollable movemtent is one result, but cognitive deficits in executive function (frontal lobe), attention (frontal-temporal-parietal lobes with sub-cortical structures), working memory (subcortical structures), among others (sequencing, regulation, perception, and episodic memory). (2,3).

One real problem facing the neuroclinician is the early testing. Since there is a 50/50 chance of carrying the mutation when a parent is diagnosed with HD, a person can be checked; but that means 100 percent occurance if carrying the mutation. In early surveys before testing procedures were possible, a rather high number of respondents answered that they'd take the test, but when it became possible and sure, that actual results amounted to only some 16 per cent actually doing it. (I mean, if you were told today, that in 20 years you would absolutely be a non-operative dementia patient {which is what it usually boils down to, although no clinician in their right mind would ever put it that way} with little hope of even prolonging that, how would it effect that 20 years to follow?)

As for the purpose of this thread, however (and jumping a number of detailed explanations on what's working (or NOT working) in brain tissue), we can very easily see that the projection of the neurons (this synaptic sea of bubbling activity) makes the person. We can see once again how brain build/state works toward keeping a whole together in what we can call the normal brain build/state (withstanding even philosophical objection)--there is a range we can call 'normal.' When these neuronal structures are altered as they are in HD, we find that the normal brain build/state, thus, by extension the normal person (as related to that which that individual brain projects) is altered.

The basal ganglia area will also be found to be altered in cases (and there is overlap) of ADHD, Autism, OCD, ADD, PD/HD, Tourette, and some addiction. I may touch on some of these others along the way too. Then, as a number of areas have been presented and explained, how this data and understanding bears on earlier considered elements of things like the soul, the spirit (which is the same in this case by definition), the mind, the self, and personhood...among some possible others.






1. Harper P.S. (2003) Huntington's Disease. IN: (Cooper ed.)Nature Encyclopedia of the Human Genome vol 3, pp 387-391. Nature Publishing Group.

Lipe, Hillary, and Bird, Thomas (2009) Late onset Huntington's Disease: Clinical and genetic characteristics of 34 cases. Journal of the Neurological Sciences 276(1,2), pp 159-162.

Runne, Heike, et al. (2008) Dysregulation of Gene Expression in Primary Neuron Models of Huntington's Disease Shows That Poyglutamine-Related Effects on the Striatal Transcriptome May Not Be Dependent on Brain Circuitry. The Journal of Neuroscience 28(39) pp 9723-9731.​

2. Craufurd, D. (2003) Huntington Disease: Predictive Genetic Testing. IN: (Cooper ed.)Nature Encyclopedia of the Human Genome vol 3, pp 392-395. Nature Publishing Group.

Ghilardi, M.F. et al. (2008) Implicit and explicit aspects of sequence learning in pre-symptomatic Huntington's disease. Parkinsonism and Related Disorders 14(6), pp 457-464.​

3. Strand, A.D., et al. (2007) Expression Profiling of Huntington's Disease Models Suggests That Brain-Derived Neurotrophic Factor Depletion Plays a Major Role in Striatal Degeneration. The Journal of Neuroscience 27(43), pp 11758-11767.

Gomez-Anson, B., et al. (2009) Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease relates to visuomotor performance and CAG number. Parkinsonism and Related Disorders 15(3), pp 213-219.

Tabriizi, Sarah J., et al. (2011) Biologial and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet 10(1), pp 31-42.​

 

[Mars Man]

Memory

Memory is perhaps a good area to go into next. One prime reason for this is the fact that memory is what essentially builds to 'self.' While it may be but only impossible to do so, if you were to push your reasonable and pragmatic (and philosophical) imagination, I would think that maybe you could understand just how it would make sense to say that by memory--over all, here--we experience the degree of self (for the most part). If we check the definition of the noun memory in a good dictionary, we will get a good working definition--but we basically do not even need to do that.

Here, as always, level of analysis is of importance, but in order to maintain our practical level which I have hoped to keep through out this thread, I will deal with the synaptic level upwards, while making mention of the bio-chemical elements needed to have our definition of memory be. Before that, however, let me simply list the categories of memory:

non-cognitive (or, automatic) and cognitive memory.
implicit (non-declarative/sub-conscious) memory, and explicit (declarative/conscious) memory.
short term memory and long term memory.
episodic (event) memory, semantic (fact/notion) memory, and perceptual memory.
biographical self memory, and metacognitive memory. (and there are a few other more precisely defined types)(1)​

One interesting, slightly humorous, element of memory is that we can see how 'what you don't know can hurt you.' A very important matter of memory, as per our general overall definition here, is that you can't have it without certain connected, integrated, and reentry processing brain structures. Additionally, to test memory functions and processes (as well as areas), we need the opposite--namely what memory is not. I will pull this out over a number of posts.

Moscovitch, Morris, et al. (2007) Learning and Memory. IN: (Baars, and Gage eds.) Cognition, Brain, and Consciousness: Introduction to Cognitive Science, pp 255-291. San Diego, CA: Academic Press.

Shrager, Yael, and Squire, Larry R. (2009) Medial Temporal Lobe Function and Human Memory. IN: (Gazzaniga ed.) The Cognitive Neurosciences 4th Ed. pp 675-690.

 

[Tsuyoiko]

I'd be interested if you could touch on something I mentioned in The Reincarnation thread, i.e., the unreliability of memory. What understanding is there of why people are often mistaken about what they remember?